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Lung protective strategy: Many pieces of the puzzle
Journal of Critical Care (2011) 26, 152–154
Lung protective strategy: Many pieces of the puzzle
Positive pressure ventilation has evolved from its mid 20th century roots as a relatively simple tool to support patients with normal lungs and abnormal neuromuscular function (ie, intraoperative neuromuscular blockade or poliomyelitis) into the present day where it is a much more complex means by which to support patients with relatively normal neuromuscular function and severely impaired pulmonary function [1]. This transition has raised many controversies, but with time, clarity emerges as we answer old questions and ask new ones. Sometimes, we must ask questions more than once before truth is revealed; moreover, even when truth is evident, it often takes time for consistent and widespread adoption of new practice to take place. In this issue of the Journal, Chaiwat et al [2] have presented a focused, albeit retrospective, investigation into this shortcoming of medicine and have tried to define some of the resulting consequences. As is true of much of what we do, the answers, and even the questions, are not so straightforward. The authors identified that, of the patients meeting the clinical criteria for acute respiratory distress syndrome (ARDS) in their institution, only about half of them received what would be considered optimal, 21st century ventilator management. Although their focus was on intraoperative practices, they also clearly documented disparity in the locale and situations where expected clinical standards were and were not delivered. Regarding the intraoperative approach, they found that the lack of adherence to generally accepted “best practices” seemed to generate no substantive difference in any discernable or clinically relevant parameters. The obvious question is “why?”
1. Tidal volume The premise that a successful lung protective strategy is predicated exclusively on the application of a specific low tidal volume (Vt) is incomplete. In the most widely quoted Acute Respiratory Distress Syndrome Network (ARDS-net) study [3], it is true that Vts were limited in the experimental group; however, plateau pressure (Ppl) was a significant 0883-9441/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.jcrc.2011.01.003
determinant of how the Vt was adjusted in both the control and experimental groups. In this work, Vt was titrated to a Ppl and patient dyspnea, with an allowable Vt of up to 8 mL/kg (ideal body weight), with Ppl remaining below 30 cm H2O. The Vts (±SD) at days 1, 2, and 7 were 6.2 ± 0.9, 6.2 ± 1.1, and 6.5 ± 1.4, respectively. Considering the SDs, patients were treated with Vts exceeding 7 mL/kg and some approaching 8 mL/kg. Because lung pathology in ARDS is far from homogeneous, different lung regions will have variable compliance characteristics and different time constants and will expand differentially depending upon their individual characteristics [4]. As Gattinoni et al [5] point out in their recent and rather cogent review of the anatomical and physiologic framework of ventilator-induced lung injury (VILI), “high tidal volume induces VILI by augmenting the pressure heterogeneity at the interface between open and constantly closed units … [and] VILI occurs only when a given threshold is exceeded.” These authors also emphasize that lung expansion force can be divided into 3 components: (1) the force needed to overcome alveolar surface tension, (2) the force required to distend the lung fibrous tension, and (3) the force necessary to expand the chest wall. Hence, the safety or harmful effects of a particular Vt or airway pressure are dependent on several factors, including the underlying character of the lung and the chest wall [5,6]. Providing that ventilation is delivered within the physiologic limits of the lung and the total lung capacity is not exceeded, mechanical ventilation is likely to be safe. Transpulmonary pressure is arguably the most effective means by which to assess safe ventilator limits; however, it will often be difficult to determine this measurement, and there will likely be regional lung differences [7]. It would seem that avoidance of arbitrary Vt parameters and targeting maintenance of the easily measurable Ppl at reasonable levels (generally, ≤30 cm H2O) should make injurious overdistension less likely. In the current study [2], the authors accept a Vt of less than 6.5 mL/kg (ideal body weight and corrected for circuit compliance) as adherence to a lung protective strategy; however, we are not given intraoperative Ppl because this
Lung protective strategy: Many pieces of the puzzle parameter was not recorded. Based on the pre- and postoperative Ppl values, Vts higher than the prescribed 6.5 mL/kg (corrected) might likely have remained within the Ppl parameters of the ARDS-net study [3]; hence, these volumes may have been tolerable without exacerbating lung injury. Thus, current expectations for ventilator management may not actually have been violated intraoperatively and might explain the lack of a negative effect of “higher Vt” ventilation. In addition, there are generally 2 factors that determine the extent of injury in any circumstance: (1) the severity of the insult and (2) the duration of the insult. In the ARDS-net study [3], plasma interleukin 6 was measured as a biochemical marker of lung inflammation over time. Measurements were made at days 1 and 3, and there was a significant difference between the control and experimental (low Vt) groups at day 3, with the low-Vt group having a lower level of interleukin 6. Thus, it appears that there was greater lung inflammation in the high-Vt group. Of course, this area of study is both complex and highly dynamic; this single indicator is likely not sufficient to fully quantify the extent of lung injury [8]. However, taking the ARDS-net data for what we can, the assessments occurred over a 3-day period. In the study at hand here [2], the duration of the purported insult was a matter of hours, not days. Hence, even if the Vt-induced “insult” were sufficient to create lung injury, the duration may have been inadequate to make an overall clinically significant difference.
2. Positive end-expiratory pressure The level of positive end-expiratory pressure (PEEP) that is appropriate to support lung function in acute lung injury (ALI) and ARDS has been a matter of controversy for decades [9]. Recently, Briel et al [10] published a robust meta-analysis of studies that compared higher vs lower levels of PEEP in adults with ALI and/or ARDS. Their analysis, which used individual patient data provided by the original investigators, has both set a new standard for metaanalysis methodology and demonstrated a 4% reduction in mortality for patients who met ARDS criteria and who had higher levels of PEEP (approximately 11-15 cm H2O) applied, without the occurrence of significant adverse events. The authors point out that a cogent explanation for this finding is that appropriate levels of PEEP may “prevent atelectasis, recruit already-collapsed alveolar units, and reduce pulmonary damage by avoiding the cyclical opening and collapse of alveoli…” This is a very salient point, but we were not provided with data on intraoperative PEEP levels regarding the patients in question here [2]. Based upon pre- and postoperative data, the PEEP levels appear similar and stable. How this factor may or may not have played a role is not clear but certainly worthy of consideration in future work.
153
3. Oxygen toxicity In addition to defining the benefit of PEEP, the work of Briel et al [10] revealed significantly lower FIO2 (b0.5 at days 3 and 7) values in the higher PEEP group. Although their study was not designed to assess this as an interactive factor, the significantly lower FIO2 in the high-PEEP group may have lessened oxygen toxicity over the 7 days during which the involved patients were assessed and contributed to the more favorable outcome. FIO2 levels are frequently high variable in patients with ALI and ARDS, and the topic of oxygen toxicity is even more controversial than Vt and PEEP. Again, it has been known for decades, especially in animal models, that high FIO2 can be toxic and even fatal when exposure is prolonged [1,11]. Ventilator-associated lung injury is significantly exacerbated by hyperoxia, even when what would be considered safe inflation pressures are used [10]. When moderate hyperoxia (FIO2, 0.5) and high Vts were used in rabbits, there was histologic evidence of significantly more lung injury compared with the group using the same Vt and an FIO2 of 0.21 [12]. In addition to the histologic and inflammatory effects of hyperoxia, there is evidence that prolonged exposure to hyperoxic conditions can impair pulmonary immune responses to bacterial infections [11]. It is common for intraoperative management to include hyperoxic conditions, and largely, these are appropriate. Hyperoxic effects in humans with ALI/ARDS have not been rigorously studied. The effects of hyperoxia in other human studies of surgical infection and sepsis remain controversial [13-15]. As clinicians, we must be acutely aware of the potential toxicity that such treatment carries and be vigilant to minimize the risk as much as possible. This factor was not reported independently in the current work [2] but should be considered in future works.
4. Conclusions Patients with ALI/ARDS present to the operating suites daily for life-saving interventions, and as we continue to improve the efficacy of our therapeutic interventions, this is likely to become a more prevalent situation. The factors that determine VILI are multiple and complex. It is essential that we, as clinicians, consider as many aspects as feasible when making decisions regarding ventilator management. It appears that assessments made purely based on Vt, without consideration of the various airway pressures that are inherent to mechanical ventilation, carry the potential for misinterpretation of the broader circumstance. The appropriate levels of PEEP and FIO2 should not be glossed over. Only through comprehensive assessments and the careful development of the anesthetic plan can we ensure that our patients receive the “state-of-the-art” care that they deserve and that we are obliged to provide.
154
W. Peruzzi William Peruzzi MD, SM, FCCM (Professor & Chief) Critical Care Medicine Department of Anesthesiology Peri-operative Medicine & Pain Management University of Miami Miller School of Medicine
References [1] Shapiro BA, Peruzzi WT. Changing practices in ventilator management: a review of the literature and suggested clinical correlations. Surgery 1995;117(2):121-33. [2] Chaiwat O, Vavilala MS, Philip S, Malakouti A, Neff MJ, Deem S, et al. Intraoperative adherence to a low tidal volume ventilation strategy in critically ill patients with pre-existing acute lung injury. J Crit Care 2011 (in press). [3] The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. NEJM 2000;342(18):1301-8. [4] Rouby J, Puybasset L, Nieszkowska A, Lu Q. Acute respiratory distress syndrome: l from computed tomography of the whole lung. Crit Care Med 2003;31(4, Suppl):S285-95. [5] Gattinoni L, Protti A, Caironi P, Carlesso E. Ventilator-induced lung injury: the anatomical and physiological framework. Crit Care Med 2010;38(10, Suppl):S539-48.
[6] Chiumello D, Carlesso E, Cadringher P, et al. Lung stress and strain during mechanical ventilation for acute respiratory distress syndrome. Am J Resp Crit Care Med 2008;178:346-55. [7] Marini JJ, Gattinoni L. Ventilatory management of acute respiratory distress syndrome: a consensus of two. Crit Care Med 2004;32(1): 250-5. [8] Ware LB, Matthay MA. The acute respiratory distress syndrome. NEJM 2000;342(18):1334-49. [9] Shapiro BA, Cane RD, Harrison RA. Positive end expiratory pressure in adults with special reference to acute lung injury: a review of the literature and suggested clinical correlations. Crit Care Med 1984;12: 127-41. [10] Briel M, Meade M, Mercat A, et al. Higher vs. lower positive endexpiratory pressure in patients with acute lung injury and acute respiratory distress syndrome. JAMA 2010;303(9):865-73. [11] Altemeier WA, Sincliar SE. Hyperoxia in the intensive care unit: why more is not always better. Curr Opin Crit Care 2007;13:73-8. [12] Sincliar SE, Altemeier WA, Batute-Bello G, Chi EY. Augmented lung injury due to interaction between hyperoxia and mechanical ventilation. Crit Care Med 2004;32:2496-501. [13] Greif R, Akca O, Horn EP, et al. Supplemental perioperative oxygen to reduce the incidence of surgical-wound infection. N Engl J Med 2000; 342:161-7. [14] Pryon KO, Fahey TJ, Lien CA, Goldstein PA. Surgical site infection and the routine use of perioperative hyperoxia in general surgical population: a randomized controlled trial. JAMA 2004;291: 79-87. [15] Calzia E, Asfar P, Hauser B, et al. Hyperoxia may be beneficial. Crit Care Med 2010;38(10 suppl):S559-68.
Lung protective strategy: Many pieces of the puzzle
Positive pressure ventilation has evolved from its mid 20th century roots as a relatively simple tool to support patients with normal lungs and abnormal neuromuscular function (ie, intraoperative neuromuscular blockade or poliomyelitis) into the present day where it is a much more complex means by which to support patients with relatively normal neuromuscular function and severely impaired pulmonary function [1]. This transition has raised many controversies, but with time, clarity emerges as we answer old questions and ask new ones. Sometimes, we must ask questions more than once before truth is revealed; moreover, even when truth is evident, it often takes time for consistent and widespread adoption of new practice to take place. In this issue of the Journal, Chaiwat et al [2] have presented a focused, albeit retrospective, investigation into this shortcoming of medicine and have tried to define some of the resulting consequences. As is true of much of what we do, the answers, and even the questions, are not so straightforward. The authors identified that, of the patients meeting the clinical criteria for acute respiratory distress syndrome (ARDS) in their institution, only about half of them received what would be considered optimal, 21st century ventilator management. Although their focus was on intraoperative practices, they also clearly documented disparity in the locale and situations where expected clinical standards were and were not delivered. Regarding the intraoperative approach, they found that the lack of adherence to generally accepted “best practices” seemed to generate no substantive difference in any discernable or clinically relevant parameters. The obvious question is “why?”
1. Tidal volume The premise that a successful lung protective strategy is predicated exclusively on the application of a specific low tidal volume (Vt) is incomplete. In the most widely quoted Acute Respiratory Distress Syndrome Network (ARDS-net) study [3], it is true that Vts were limited in the experimental group; however, plateau pressure (Ppl) was a significant 0883-9441/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.jcrc.2011.01.003
determinant of how the Vt was adjusted in both the control and experimental groups. In this work, Vt was titrated to a Ppl and patient dyspnea, with an allowable Vt of up to 8 mL/kg (ideal body weight), with Ppl remaining below 30 cm H2O. The Vts (±SD) at days 1, 2, and 7 were 6.2 ± 0.9, 6.2 ± 1.1, and 6.5 ± 1.4, respectively. Considering the SDs, patients were treated with Vts exceeding 7 mL/kg and some approaching 8 mL/kg. Because lung pathology in ARDS is far from homogeneous, different lung regions will have variable compliance characteristics and different time constants and will expand differentially depending upon their individual characteristics [4]. As Gattinoni et al [5] point out in their recent and rather cogent review of the anatomical and physiologic framework of ventilator-induced lung injury (VILI), “high tidal volume induces VILI by augmenting the pressure heterogeneity at the interface between open and constantly closed units … [and] VILI occurs only when a given threshold is exceeded.” These authors also emphasize that lung expansion force can be divided into 3 components: (1) the force needed to overcome alveolar surface tension, (2) the force required to distend the lung fibrous tension, and (3) the force necessary to expand the chest wall. Hence, the safety or harmful effects of a particular Vt or airway pressure are dependent on several factors, including the underlying character of the lung and the chest wall [5,6]. Providing that ventilation is delivered within the physiologic limits of the lung and the total lung capacity is not exceeded, mechanical ventilation is likely to be safe. Transpulmonary pressure is arguably the most effective means by which to assess safe ventilator limits; however, it will often be difficult to determine this measurement, and there will likely be regional lung differences [7]. It would seem that avoidance of arbitrary Vt parameters and targeting maintenance of the easily measurable Ppl at reasonable levels (generally, ≤30 cm H2O) should make injurious overdistension less likely. In the current study [2], the authors accept a Vt of less than 6.5 mL/kg (ideal body weight and corrected for circuit compliance) as adherence to a lung protective strategy; however, we are not given intraoperative Ppl because this
Lung protective strategy: Many pieces of the puzzle parameter was not recorded. Based on the pre- and postoperative Ppl values, Vts higher than the prescribed 6.5 mL/kg (corrected) might likely have remained within the Ppl parameters of the ARDS-net study [3]; hence, these volumes may have been tolerable without exacerbating lung injury. Thus, current expectations for ventilator management may not actually have been violated intraoperatively and might explain the lack of a negative effect of “higher Vt” ventilation. In addition, there are generally 2 factors that determine the extent of injury in any circumstance: (1) the severity of the insult and (2) the duration of the insult. In the ARDS-net study [3], plasma interleukin 6 was measured as a biochemical marker of lung inflammation over time. Measurements were made at days 1 and 3, and there was a significant difference between the control and experimental (low Vt) groups at day 3, with the low-Vt group having a lower level of interleukin 6. Thus, it appears that there was greater lung inflammation in the high-Vt group. Of course, this area of study is both complex and highly dynamic; this single indicator is likely not sufficient to fully quantify the extent of lung injury [8]. However, taking the ARDS-net data for what we can, the assessments occurred over a 3-day period. In the study at hand here [2], the duration of the purported insult was a matter of hours, not days. Hence, even if the Vt-induced “insult” were sufficient to create lung injury, the duration may have been inadequate to make an overall clinically significant difference.
2. Positive end-expiratory pressure The level of positive end-expiratory pressure (PEEP) that is appropriate to support lung function in acute lung injury (ALI) and ARDS has been a matter of controversy for decades [9]. Recently, Briel et al [10] published a robust meta-analysis of studies that compared higher vs lower levels of PEEP in adults with ALI and/or ARDS. Their analysis, which used individual patient data provided by the original investigators, has both set a new standard for metaanalysis methodology and demonstrated a 4% reduction in mortality for patients who met ARDS criteria and who had higher levels of PEEP (approximately 11-15 cm H2O) applied, without the occurrence of significant adverse events. The authors point out that a cogent explanation for this finding is that appropriate levels of PEEP may “prevent atelectasis, recruit already-collapsed alveolar units, and reduce pulmonary damage by avoiding the cyclical opening and collapse of alveoli…” This is a very salient point, but we were not provided with data on intraoperative PEEP levels regarding the patients in question here [2]. Based upon pre- and postoperative data, the PEEP levels appear similar and stable. How this factor may or may not have played a role is not clear but certainly worthy of consideration in future work.
153
3. Oxygen toxicity In addition to defining the benefit of PEEP, the work of Briel et al [10] revealed significantly lower FIO2 (b0.5 at days 3 and 7) values in the higher PEEP group. Although their study was not designed to assess this as an interactive factor, the significantly lower FIO2 in the high-PEEP group may have lessened oxygen toxicity over the 7 days during which the involved patients were assessed and contributed to the more favorable outcome. FIO2 levels are frequently high variable in patients with ALI and ARDS, and the topic of oxygen toxicity is even more controversial than Vt and PEEP. Again, it has been known for decades, especially in animal models, that high FIO2 can be toxic and even fatal when exposure is prolonged [1,11]. Ventilator-associated lung injury is significantly exacerbated by hyperoxia, even when what would be considered safe inflation pressures are used [10]. When moderate hyperoxia (FIO2, 0.5) and high Vts were used in rabbits, there was histologic evidence of significantly more lung injury compared with the group using the same Vt and an FIO2 of 0.21 [12]. In addition to the histologic and inflammatory effects of hyperoxia, there is evidence that prolonged exposure to hyperoxic conditions can impair pulmonary immune responses to bacterial infections [11]. It is common for intraoperative management to include hyperoxic conditions, and largely, these are appropriate. Hyperoxic effects in humans with ALI/ARDS have not been rigorously studied. The effects of hyperoxia in other human studies of surgical infection and sepsis remain controversial [13-15]. As clinicians, we must be acutely aware of the potential toxicity that such treatment carries and be vigilant to minimize the risk as much as possible. This factor was not reported independently in the current work [2] but should be considered in future works.
4. Conclusions Patients with ALI/ARDS present to the operating suites daily for life-saving interventions, and as we continue to improve the efficacy of our therapeutic interventions, this is likely to become a more prevalent situation. The factors that determine VILI are multiple and complex. It is essential that we, as clinicians, consider as many aspects as feasible when making decisions regarding ventilator management. It appears that assessments made purely based on Vt, without consideration of the various airway pressures that are inherent to mechanical ventilation, carry the potential for misinterpretation of the broader circumstance. The appropriate levels of PEEP and FIO2 should not be glossed over. Only through comprehensive assessments and the careful development of the anesthetic plan can we ensure that our patients receive the “state-of-the-art” care that they deserve and that we are obliged to provide.
154
W. Peruzzi William Peruzzi MD, SM, FCCM (Professor & Chief) Critical Care Medicine Department of Anesthesiology Peri-operative Medicine & Pain Management University of Miami Miller School of Medicine
References [1] Shapiro BA, Peruzzi WT. Changing practices in ventilator management: a review of the literature and suggested clinical correlations. Surgery 1995;117(2):121-33. [2] Chaiwat O, Vavilala MS, Philip S, Malakouti A, Neff MJ, Deem S, et al. Intraoperative adherence to a low tidal volume ventilation strategy in critically ill patients with pre-existing acute lung injury. J Crit Care 2011 (in press). [3] The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. NEJM 2000;342(18):1301-8. [4] Rouby J, Puybasset L, Nieszkowska A, Lu Q. Acute respiratory distress syndrome: l from computed tomography of the whole lung. Crit Care Med 2003;31(4, Suppl):S285-95. [5] Gattinoni L, Protti A, Caironi P, Carlesso E. Ventilator-induced lung injury: the anatomical and physiological framework. Crit Care Med 2010;38(10, Suppl):S539-48.
[6] Chiumello D, Carlesso E, Cadringher P, et al. Lung stress and strain during mechanical ventilation for acute respiratory distress syndrome. Am J Resp Crit Care Med 2008;178:346-55. [7] Marini JJ, Gattinoni L. Ventilatory management of acute respiratory distress syndrome: a consensus of two. Crit Care Med 2004;32(1): 250-5. [8] Ware LB, Matthay MA. The acute respiratory distress syndrome. NEJM 2000;342(18):1334-49. [9] Shapiro BA, Cane RD, Harrison RA. Positive end expiratory pressure in adults with special reference to acute lung injury: a review of the literature and suggested clinical correlations. Crit Care Med 1984;12: 127-41. [10] Briel M, Meade M, Mercat A, et al. Higher vs. lower positive endexpiratory pressure in patients with acute lung injury and acute respiratory distress syndrome. JAMA 2010;303(9):865-73. [11] Altemeier WA, Sincliar SE. Hyperoxia in the intensive care unit: why more is not always better. Curr Opin Crit Care 2007;13:73-8. [12] Sincliar SE, Altemeier WA, Batute-Bello G, Chi EY. Augmented lung injury due to interaction between hyperoxia and mechanical ventilation. Crit Care Med 2004;32:2496-501. [13] Greif R, Akca O, Horn EP, et al. Supplemental perioperative oxygen to reduce the incidence of surgical-wound infection. N Engl J Med 2000; 342:161-7. [14] Pryon KO, Fahey TJ, Lien CA, Goldstein PA. Surgical site infection and the routine use of perioperative hyperoxia in general surgical population: a randomized controlled trial. JAMA 2004;291: 79-87. [15] Calzia E, Asfar P, Hauser B, et al. Hyperoxia may be beneficial. Crit Care Med 2010;38(10 suppl):S559-68.